Vitamin K status has no influence on the effect of vitamin D supplementation on bone turnover and cardiovascular markers: a randomized controlled trial

Background/objectives Vitamin K and D co-treatment may have additive effects on bone and cardiovascular health and is frequently used as an over-the-counter supplement. The primary aim of this study was to assess whether the effect of vitamin D supplementation on bone turnover markers and cardiovascular parameters is modified according to vitamin K status at baseline (i.e., serum levels of vitamin K1, MK4 and MK7). Methods This is a post-hoc analysis of a randomized controlled vitamin D supplementation (2,800 international units daily for 8 weeks) trial in 200 participants. We measured vitamin K1, MK4 and MK7 by means of the currently available gold standard liquid chromatography tandem mass spectrometric and analysed cardiovascular and bone markers (including 24-h systolic and diastolic blood pressure, glucose and lipid parameters as well as osteocalcin, beta-crosslaps, and procollagen type 1 N-terminal propeptide). The main aim was to analyze whether pre-intervention vitamin K status (moderator) influenced the effects of vitamin D supplementation on outcome measures of bone and cardiovascular health after the intervention (moderation analyses). We also investigated whether vitamin D supplementation effects vitamin K status and whether vitamin K measures correlated with the outcome parameters. Results Moderation analyses showed no significant interaction between vitamin K status and the intervention (vitamin D supplementation/placebo) on cardiovascular or bone parameters. We observed no treatment effect of vitamin D on vitamin K status. In exploratory analyses, parameters of vitamin K status correlated only weakly and inconsistently with some bone and cardiovascular parameters. Conclusion The data from this post-hoc analysis do not provide evidence for the assumption that vitamin K status modifies or enhances effects of vitamin D supplementation on cardiovascular or bone parameters. These findings are in line with current guidelines, which do not routinely recommend vitamin K and D co-treatment in patients with osteoporosis. However, further trials are needed to evaluate the potential benefits of vitamin K supplementation and its combination with vitamin D.